Mature T-Cell and NK-Cell Neoplasm (BSH 2011)

Intro

 

  • Guideline refers to lymphomas by WHO 2008 classification, watch out for differences

  • Mature or peripheral T-cell neoplasms are biologically and clinically varied

  • Result from clonal proliferation of post-thymic lymphocytes

  • Good prognosis = Anaplastic Lymphoma Kinase (ALK) positive anaplastic large cell (ALCL)

  • Most nodal and extra-nodal T-cell lymphomas however have 30% 5-year survival

  • Rare and lack phase 3 trial data due to low numbers.

 

WHO 2016 Classification

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Epidemiology

 

10% of lymphoid malignancies

Incidence 1.7 / 100,000 / year

NK-Cell lymphomas more common in Asia and associated with EBV

Adult T-Cell leukaemia/lymphoma (ATL) associated with HTLV-1

 

Presentation & Diagnosis

 

Often present late with advanced stage, poor performance status and extra-nodal disease

Para-neoplastic features seen – eosinophilia, HLH, autoimmune processes

FBC, Biochem, LDH, B2M, CXR, CT, BM Biopsy

Role of PET-CT still under investigation

 

Mature T-Cell Leukaemias

 

T-Prolymphocytic Leukaemia (T-PLL)

 

  • Post-Thymic T-cell malignancy.

  • Association with ataxia telangiectasia

  • 10-15% pt have an indolent phase then clinically aggressive disease with WBC >100, serous effusions, skin infiltration, splenomegaly and lymphadenopathy

  • Mature T cell markers – CD2+, CD3 weak+, CD5+, CD7+

  • OS 7 months

  • 1st line therapy: IV Alemtuzumab. Transplant in first remission.

  • (Marsden Hospital Cohort – 125 pt. Rx’d with IV Campath. CR 50%, PR21%. Median OS 16 months. 5-yr OS 32% for transplanted patients (mix of allo and auto))

 

T-Large Granular Lymphocytic Leukaemia (T-LGL)

 

  • Persistent clonal expansion of T (80%) or NK cells

  • Associated with AI disorders, e.g. rheumatoid arthritis

  • Indolent, median survival >10 years

  • Most patients develop severe neutropenia (soluble Fas ligand released from LGL’s induces neutrophil apoptosis)

  • Markers – CD3+, TCRαβ+, CD8+, CD16+, CD57+, CD94+, KIR+, CD56-

  • STAT3 mutation in 30-40% (occurs as a 2o event in an already expanding clone)

  • Treat if complications from cytopenias

  • 1st line: Ciclosporin or low dose methotrexate + GCSF/Epo

  • Goal of Rx: Reducing or silencing clone will restore counts. Not necessary to eliminate it.

 

Aggressive NK-cell leukaemia

 

  • More common in Asia and almost always associated with EBV

  • Acute presentation with fever, jaundice, LNadenopathy, organomegaly

  • Patients are sick, may have DIC / HLH / MOF

  • Markers – CD3episilon+, CD56+, CD16+, CD2-, sCD3-, CD57-

  • OS 2 months

  • 1st line: Clinical trial, ALL-type therapy

 

Adult T-Cell Lymphoma (ATL)

 

  • Caused by HTLV-1, which is epidemic in Japan, Africa, South America

  • Check for strongyloides at diagnosis

  • 4 subtypes – leukaemic, lymphoma, chronic & smouldering

  • Markers – CD4+, CD25+, CD7-

  • 1st line therapy depends on type

    • Smouldering & Chronic – anti-retrovirals +/- monoclonal antibodies

    • Lymphoma – CHOP + antivirals + monoclonal antibodies

    • Leukaemia - CHOP + antivirals + monoclonal antibodies. Then Transplant

 

Nodal PTCL

 

Peripheral T-Cell Lymphoma, NOS (PTCL-NOS)

 

  • Largest group, 50% of T-cell cases

  • Aggressive, usually nodal

  • 1st line therapy: Clinical trial, otherwise CHOP but disappointing results. Autograft in 1st CR.

 

Angio-Immunoblastic T Cell Lymphoma (AITL)

 

  • A disease of the elderly

  • Presentation often mimics an infectious process

  • Sometimes spontaneously regresses

  • OS 30% at 5-years

  • 1st line therapy: Trial, otherwise CHOP or FC

 

Anaplastic Large Cell Lymphoma (ALCL)

 

  • Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase, usually only found in CNS.

  • NPM1-ALK fusion gene defines ALK+ ALCL

  • ALK+ significantly better prognosis than ALK-. Though ALK- still better than PTCL-NOS

  • 1st line therapy: Clinical trial or CHOP. Autograft

  • Cutaneous ALCL can have local excision +/- radiotherapy

 

Extra-Nodal PTCL

 

Extranodal NK/T-Cell Lymphoma, nasal type

 

  • Aggressive, EBV associated

  • Presents in nasal structure but nodal or BM involvement can be present

  • Presents as adult male with facial oedema, nasal obstruction and epistaxis

  • 1st line therapy: Trial, otherwise CHOP + radiotherapy but this is unsatisfactory

 

Enteropathy-Associated T-Cell Lymphoma (EATL)

 

  • Aggressive large cell tumour of the small bowel

  • Associated with HLA-DQ 2or 8, and coeliac disease

  • Presents as older male with diarrhoea and abdominal pain

  • OS 7 months

  • 1st line therapy: No satisfactory treatment. CHOP + Autograft

 

Hepatosplenic T-Cell Lymphoma

 

  • Aggressive disease of young adult males

  • Associated with post solid organ transplant or immunosuppression

  • OS 16 months

  • 1st line therapy: No satisfactory recommendations can be made

 

Subcutaneous pannciulitis-like T-Cell Lymphoma (SPTCL)

 

  • Presents as subcutaneous tumour nodules at any age.

  • Not universally aggressive. Consider CHOP / radiotherapy